Interest in alpha-emitting radioisotopes for therapeutic applications, especially the treatment of cancer using highly selective biological vectors, has grown steadily in recent years. Unfortunately, their development as anti-cancer agents has been hindered by the lack of a readily expandable supply chain. This is particularly true for Ac-225 (t1/2=9.92 d, 100% α) and its daughter proposed for generator harvest, Bi-213 (t1/2=45.6 min, 98% β-, 2% α), the availability of which has been predicated upon harvest from legacy stores of their shared, long-lived parent, Th-229. See FIGS. 1A-1C. The global feedstock of Th-229 is derived from molten thorium-salt breeder reactors, which produced fissile U-233 for reactor and weapons applications. With the growing need to secure quantities of special nuclear materials, future reactor production and dissemination of the U-233 parent of Ac-225 is extremely unlikely. Meanwhile, the current annual Ac-225 supply of approximately 1.7 Ci, which is distributed between United States, European, and Russian institutions, is unable to support large-scale clinical trials.
Modern theoretical comparisons of the cell-killing potential of various nuclides point encouragingly to Ac-225, whose daughters emit four highly energetic a-particles while decaying to stable Bi-209 and buttress policy directives at the national and international levels. Recent reports establish that proton irradiation of thorium targets are able to produce Curie-quantities of approximately 2 Ci (74 GBq) of Ac-225 in a single week's bombardment.
But concurrent with Ac-225 generation is the formation of undesirable radioisotopes. In particular, Ac-226 and Ac-227 are problematic because they follow the chemistry of Ac-225 in any chemical separation. Their removal requires mass separation techniques, which are cost prohibitive and have a throughput efficiency for Ac-225 that is likely to be <20%.
In addition, radioactive isotopes of lower lanthanide elements (lanthanum and cerium) limit the medical utility of the Ac-225 product of accelerator irradiations and removal of these isotopes from actinium is extremely challenging because of chemical similarities between actinium, lanthanum, and cerium.
As such, improved methods for the generation and purification of Ac-225 are needed.